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The impact of thalamic stimulation on activities of daily living for essential tremor.

BACKGROUND: Deep Brain Stimulation (DBS) of the ventro-intermedius nucleus of the thalamus is the treatment of choice for drug-refractory essential tremor (ET). This study evaluated the effectiveness of thalamic stimulation in improving the patient's quality of life through activities of daily living. METHODS: Sixteen ET patients completed a health questionnaire, the "Tremor Activities of Daily Living Scale" (TADLS) measured by the patient, a 10-item subset of the TADLS measured by the clinician, and the Fahn-Tolosa-Marin tremor rating scale (TRS). Each patient was evaluated with the stimulator on and off with the average evaluation occurring 13 months after surgery. Additionally, improvements on the TADLS were compared to electrode positioning on the axial plane and stimulation parameters. RESULTS: There was a 44.0% improvement in the patient-rated TADLS, a 45.2% improvement in the clinician-rated TADLS, and a 33.9% improvement in the TRS. The average electrode location was 5.65 mm anterior to the posterior commissure (AC-PC), 13.4 mm lateral from the midline, and 2.0 mm below the AC-PC line. The average stimulation parameters were 2.74 Volts, 160 Hertz, and 119 microsec. There was no correlation between improvements on the TADLS, electrode location, and stimulation parameters. Of the 16 patients, 10 patients would repeat the surgery, two were unsure, and four would not repeat the surgery. CONCLUSIONS: Tremor is significantly controlled with DBS and activities of daily living are highly correlated with patient satisfaction. The degree of improvement in the four patients who would not repeat the surgery was outweighed by the negative factors associated with the surgery.

Activities of Daily Living↗

A comparison of continuous thalamic stimulation and thalamotomy for suppression of severe tremor.

BACKGROUND: Deep-brain stimulation through an electrode implanted in the thalamus was developed as an alternative to thalamotomy for the treatment of drug-resistant tremor. Stimulation is thought to be as effective as thalamotomy but to have fewer complications. We examined the effects of these two procedures on the functional abilities of patients with drug-resistant tremor due to Parkinson's disease, essential tremor, or multiple sclerosis. METHODS: Sixty-eight patients (45 with Parkinson's disease, 13 with essential tremor, and 10 with multiple sclerosis) were randomly assigned to undergo thalamotomy or thalamic stimulation. The primary outcome measure was the change in functional abilities six months after surgery, as measured by the Frenchay Activities Index. Scores for this index can range from 0 to 60, with higher scores indicating better function. Secondary outcome measures were the severity of tremor, the number of adverse effects, and patients' assessment of the outcome. RESULTS: Functional status improved more in the thalamic-stimulation group than in the thalamotomy group, as indicated by increases in the score for the Frenchay Activities Index (from 31.4 to 36.3 and from 32.0 to 32.5, respectively; difference between groups, 4.4 points; 95 percent confidence interval, 2.0 to 6.9). After adjustment for base-line characteristics, multivariate analysis also showed that the thalamic-stimulation group had greater improvement (difference between groups, 5.1 points; 95 percent confidence interval, 2.3 to 7.9). Tremor was suppressed completely or almost completely in 27 of 34 patients in the thalamotomy group and in 30 of 33 patients in the thalamic-stimulation group. One patient in the thalamic-stimulation group died perioperatively after an intracerebral hemorrhage. With the exception of this incident, thalamic stimulation was associated with significantly fewer adverse effects than thalamotomy. Functional status was reported as improved by 8 patients in the thalamotomy group, as compared with 18 patients in the thalamic-stimulation group (P=0.01). CONCLUSIONS: Thalamic stimulation and thalamotomy are equally effective for the suppression of drug-resistant tremor, but thalamic stimulation has fewer adverse effects and results in a greater improvement in function.

Activities of Daily Living↗

Effect of motor improvement on quality of life following subthalamic stimulation is mediated by changes in depressive symptomatology.

BACKGROUND/AIMS: Subthalamic deep brain stimulation (STN-DBS) for Parkinson's disease (PD) improves motor symptoms and quality of life (QOL). Because depression is a potent correlate of QOL, and STN-DBS may be associated with changes in mood, this study sought to determine whether QOL improvement is a direct or indirect consequence of motor improvement. METHODS: 26 patients with PD, free of dementia and major depression, who consecutively underwent bilateral, microelectrode-guided STN-DBS, underwent preoperative and 3-month postoperative neuropsychological evaluation, including measures of QOL (PD Questionnaire -39) and depressive symptoms (Beck Depression Inventory). RESULTS: Motor score in the Unified Parkinson's Disease Rating Scale (UPDRS Part III) improved significantly with STN-DBS relative to preoperative 'on' and 'off' scores, as did QOL and depressive symptoms. Extent of QOL improvement tended to be associated with improvement in motor score from presurgical on to postsurgical on stimulation and on medication state. QOL improvement was significantly related to amelioration of depressive symptoms. Partial correlations revealed that the association between QOL improvement and depression remained significant when influence of motor improvement on QOL and depression was controlled for. The motor-QOL association was no longer significant when effects of depression were controlled for. CONCLUSIONS: Significant QOL improvements after STN-DBS are associated with improved motor 'on' state and depressive symptoms. The influence of motor improvement on QOL may be largely indirect by reducing depression.

Aged↗

[Parkinson's disease: the disease concept, etiology and diagnostic bases].

Parkinson's disease (PD) is caused by degeneration of nigral dopaminergic neurons. This results in dysfunction of the basal ganglia, thereby exhibiting movement disorders. The four cardinal signs of PD include bradykinesia, rigidity, resting tremor and postural instability. In the majority of patients with PD, the four cardinal signs are ameliorated by levodopa. In addition to anti-parkinson medication, surgery of the basal ganglia for PD has been applied. Local electrical stimulation of particular nuclei of the basal ganglia (deep brain stimulation) for PD has also proved to give satisfactory outcome. Both genetic and environment factors are considered to contribute to the initiation of PD. Some mutations of particular genes (e.g., alpha-synuclein) are found to link to parkinsonian families.

Aged↗

Effects of bilateral subthalamic stimulation on cognitive function in Parkinson disease.

BACKGROUND: Chronic bilateral subthalamic deep brain stimulation (STN-DBS) is known to improve motor function in patients with Parkinson disease (PD). However, the possible effects of STN-DBS on neuropsychological functions have been studied less. OBJECTIVE: To investigate the effects of STN-DBS on neuropsychological functions in PD. DESIGN: Before-after trial. PATIENTS AND METHODS: Fifteen consecutive patients were assessed before and 3 months after implantation of stimulators for STN-DBS (postsurgical assessment with the stimulators switched on). Both assessments were performed with patients in a drug-free condition. The neuropsychological battery consisted of tests measuring memory and visuospatial and frontal functions. RESULTS: The comparison between presurgical and postsurgical performance showed a moderate deterioration in verbal memory and prefrontal and visuospatial functions, and a moderate improvement in a prefrontal task and obsessive-compulsive traits. The motor state improved in all patients. CONCLUSION: Therapy with STN-DBS improves motor symptoms in PD without any clinically relevant neuropsychological deterioration.

Aged↗

Long-lasting microthalamotomy effect after temporary placement of a thalamic stimulating electrode.

Essential tremor can be surgically treated by thalamotomy or deep brain stimulation. During the surgical procedure for both of these procedures, a transient microthalamotomy effect has been observed. This benefit is usually short-lived and appears to be predictive of patient outcome. This report describes a patient who underwent a temporary placement of a stimulating electrode within the ventral intermediate nucleus of the motor thalamus. The procedure was aborted intraoperatively and the patient demonstrated a microthalamotomy effect. This microthalamotomy effect has remained persistent for 24 months, and the patient remains tremor free. This case report lends evidence to the idea that the volume of motor thalamus responsible for tremor may be small and precise. By recognizing the benefit obtained from small lesions with minimal tissue manipulation, surgeons can continue to refine the target for movement disorder surgery.

Electric Stimulation Therapy↗

[Pallidal and subthalamic stimulation in Parkinson's disease: lessons from the unsatisfactory results].

BACKGROUND: Deep brain stimulation is being widely used in advanced Parkinson's disease (PD). Outcome determinants are not known. OBJECTIVE: Some relevant data about outcome may be obtained from the study of patients with unsatisfactory results. PATIENTS AND METHODS: We have retrospectively analyzed the number and causes of unsatisfactory results (insufficient improvement 6 months after the intervention) in 211 patients. RESULTS: Forty patients (18.9%) experienced an unsatisfactory result. Inadequate clinical selection by advanced age, abnormal MRI and levodopa unresponsive symptoms was the main cause in 28 cases. In 11 patients a misplacement of the electrode was reported. In 2 cases no cause was identified. Thirty-four out of the 40 patients corresponded to the early experience of the teams involved in the study. CONCLUSION: We conclude that the main factors responsible for a negative outcome are related to the inadequate clinical selection of the patients and the incorrect placement of the electrode. The experience of the team may also be a key factor.

Aged↗

Reversibility of chronic neurologic deficits. Some effects of electrical stimulation of the thalamus and internal capsule in man.

Stimulation of the thalamus and internal capsule with Medtronic deep brain stimulation electrodes produced improvement in pain, hemiparesis, dystonia, torticollis, tremor. speech impairment and epilepsy. Stimulation at voltages above or below clinically effective levels (e.g., 6 V, 0.3 ms, 74 Hz) resulted in a loss of clinical efficacy. Somatosensory evoked responses (short and long latency) and depth electrode recordings were helpful in localisation and 'biocalibration' of electrical stimulation.

Adult↗

Postoperative management of subthalamic nucleus stimulation for Parkinson's disease.

The postoperative neurologic management of patients with deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson' s disease is a complex dynamic process that involves a progressive increase in stimulation intensity and a parallel decrease in antiparkinsonian medication while assessing the interactions of both treatments. Neurologists responsible for postoperative management of patients receiving STN DBS must have expert knowledge of the electroanatomy of the subthalamic area and be familiar with the medical treatment of motor and nonmotor symptoms, including the management of long-term complications of levodopa treatment. Neurosurgeons who perform DBS need to understand the principles that guide the postoperative adaptation of treatment. This article defines guidelines for setting stimulation parameters, adapting drugs and managing adverse effects.

Antiparkinson Agents↗

Effects of subthalamic nucleus stimulation and medication on resting and postural tremor in Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and antiparkinsonian medication have proved to be effective treatments for tremor in Parkinson's disease. To date it is not known how and to what extent STN DBS alone and in combination with antiparkinsonian medication alters the pathophysiology of resting and postural tremor in idiopathic Parkinson's disease. The purpose of this study was to examine the effects of STN DBS and antiparkinsonian medication on the neurophysiological characteristics of resting and postural hand tremor in Parkinson's disease. Resting and postural hand tremor were recorded using accelerometry and surface electromyography (EMG) from 10 Parkinson's disease patients and 10 matched control subjects. The Parkinson's disease subjects were examined under four treatment conditions: (i) off treatment; (ii) STN DBS; (iii) medication; and (iv) medication plus STN DBS. The amplitude, EMG frequency, regularity, and 1-8 Hz tremor-EMG coherence were analysed. Both STN DBS and medication reduced the amplitude, regularity and tremor-EMG coherence, and increased the EMG frequency of resting and postural tremor in Parkinson's disease. STN DBS was more effective than medication in reducing the amplitude and increasing the frequency of resting and postural tremor to healthy physiological levels. These findings provide strong evidence that effective STN DBS normalizes the amplitude and frequency of tremor. The findings suggest that neural activity in the STN is an important modulator of the neural network(s) responsible for both resting and postural tremor genesis in Parkinson's disease.

Adult↗

Activation of the anterior cingulate cortex by thalamic stimulation in patients with chronic pain: a positron emission tomography study.

OBJECT: Deep brain stimulation (DBS) of the sensory thalamus has been used to treat chronic, intractable pain. The goal of this study was to investigate the thalamocortical pathways activated during thalamic DBS. METHODS: The authors compared positron emission tomography (PET) images obtained before, during, and after DBS in five patients with chronic pain. Two of the five patients reported significant DBS-induced pain relief during PET scanning, and the remaining three patients did not report any analgesic effect of DBS during scanning. The most robust effect associated with DBS was activation of the anterior cingulate cortex (ACC). An anterior ACC activation was sustained throughout the 40 minutes of DBS, whereas a more posteriorly located ACC activation occurred at a delay after onset of DBS, although these activations were not dependent on the degree of pain relief reported during DBS. However, implications specific to the analgesic effect of DBS require further study of a larger, more homogeneous patient population. Additional effects of thalamic DBS were detected in motor-related regions (the globus pallidus, cortical area 4, and the cerebellum) and visual and association cortical areas. CONCLUSIONS: The authors demonstrate that the ACC is activated during thalamic DBS in patients with chronic pain.

Adult↗

Neuropsychological changes after subthalamic nucleus stimulation: a 12 month follow-up in nine patients with Parkinson's disease.

Deep brain stimulation of the subthalamic nucleus has been recognized as one of the most promising techniques to decrease 'off' motor symptoms and motor fluctuations, allowing a reduction of drug therapy and limiting side effects of drug therapy. However, there is still open debate on the possible consequences of chronic subthalamic stimulation on general cognitive performance. A general amelioration of cognitive performance, in particular of executive functions has been reported but results are not homogeneous. We studied nine patients with Parkinson's Disease for 12 months following surgery for deep stimulation, studying their cognitive performances, paying particular attention to linguistic tests and selective alternating words production. Our results may be consistent with a slowing of cognitive activity, with a reduction of quantitative production, but with an increase in control of linguistic production, which is more precise and definite. We discuss the possible significance of these results, fully aware that only nine patients were involved, and that the potential for generalization is seriously limited, with a particular overview on the frontal-subthalamic pathway, which in our opinion is responsible for the results we observed.

Aged↗

Microelectrode array for chronic deep-brain microstimulation and recording.

We have developed an array of microelectrodes that is suitable for long-term implantation into the subthalamic nucleus (STN) or the globus pallidus and is able to record from single neurons, as well as deliver localized microstimulation. This device can be used to investigate the mechanisms by which deep brain stimulation can ameliorate the symptoms of Parkinson's disease and other movement disorders, and also may be the basis for a new clinical tool for the treatment of Parkinson's disease, by capitalizing on the high spatial specificity of intranuclear microstimulation. The array includes 16 activated iridium microelectrodes, 5-6 mm in length, within a cluster approximately 1.8 mm in diameter. We have fabricated the array using materials carrying the USP Category VI classification, and we have developed an apparatus and a procedure for implanting the microelectrode arrays into the deep brain. Ten arrays have been implanted into the STN of domestic cats, and one into the internal segment of the globus pallidus, for 140-415 days. During that time, we were able to record action potentials from individual neurons, on 4 to 8 of the 16 channels. The microelectrode' active surface areas ranged from 500 to 2000 microm2. Controlled-current pulses, 26.5 microA in amplitude and 150 micros/phase in duration (4 nC/phase) were used to excite neurons in the cat's STN. In addition to direct activation, the stimulus modulated the neuronal activity over a distance of at least 1.2 mm from the site of stimulation. These parameters did not induce histologically detectable changes around the tip sites after 35 hours of stimulation at 100 Hz (7 hours of stimulation per day, on 5 successive days), if the electrode' active surface area was 1000 microm2 or greater.

Action Potentials↗

Motor cortex inhibition induced by acoustic stimulation.

The influence of the brainstem motor system on cerebral motor areas may play an important role in motor control in health and disease. A new approach to investigate this interaction in man is combining acoustic stimulation activating the startle system with transcranial magnetic stimulation (TMS) over the motor cortex. However, it is unclear whether the inhibition of TMS responses following acoustic stimulation occurs at the level of the motor cortex through reticulo-cortical projections or subcortically, perhaps through reticulo-spinal projections. We compared the influence of acoustic stimulation on motor effects elicited by TMS over motor cortical areas to those evoked with subcortical electrical stimulation (SES) through depth electrodes in five patients treated with deep brain stimulation for Parkinson's disease. SES bypasses the motor cortex, demonstrating any interaction with acoustic stimuli at the subcortical level. EMG was recorded from the contralateral biceps brachii muscle. Acoustic stimulation was delivered binaurally through headphones and used as a conditioning stimulus at an interstimulus interval of 50 ms. When TMS was used as the test stimulus, the area and amplitude of the conditioned motor response was significantly inhibited (area: 57.5+/-12.9%, amplitude: 47.9+/-7.4%, as percentage of unconditioned response) whereas facilitation occurred with SES (area: 110.1+/-4.3%, amplitude: 116.9+/-6.9%). We conclude that a startle-evoked activation of reticulo-cortical projections transiently inhibits the motor cortex.

Acoustic Stimulation↗

[Neurosurgery for cancer pain (author's transl)].

Neurosurgical management of cancer pain is indicated when other therapeutic methods have failed. It requires a careful investigation of all the parameters of pain and an adaptation to suit each individual case. The decision of such a treatment is as important as the chosen procedure. The psychological features must be carefully known. The surgical procedures of sectioning nervous structures (spino-thalamic cordotomy, rhizotomy), unless they are done with the help of the operating microscope, are slowly being abandoned. Percutaneous techniques under radiographic and electrophysiological control (Gasser ganglion) and cerebral stereotaxic techniques (mesencephalotomy) are there indicated. Stimulation of th dorsal columns of the spinal cord or deep brain stimulation are too recent to demonstrate a definite opinion.

Humans↗

Results of chronic subthalamic nucleus stimulation for Parkinson's disease: a 1-year follow-up study.

BACKGROUND: Deep brain stimulation (DBS) has been established as an alternative approach for the treatment of advanced Parkinson's disease (PD). Recently, the subthalamic nucleus (STN) has been identified as the optimal target for DBS. METHODS: Thirty-eight patients have undergone surgery for advanced PD since 1996. They include 12 females and 26 males with a mean age of 55.6 years. The mean stage on the Hoehn and Yahr Scale was 3.5 (off condition). Electrodes (Medtronic DBS 31389) were stereotactically implanted into the STN bilaterally. Targeting was performed using computerized tomography (CT) scans and ventriculography (VG). After 4 days of external stimulation, permanent neurostimulators were implanted. Patients were evaluated preoperatively and 1, 6, and 12 months postoperatively. Evaluations were performed in defined on and off states using the Unified Parkinson's Disease Rating Scale (UPDRS) as well as the Hoehn and Yahr Scale, the dyskinesia scale, and the Activities of Daily Living (ADL) Scale. RESULTS: Significant improvement of all motor symptoms was found in all patients (UPDRS motor score 32/48 preoperatively versus 15/30 at 12-month follow-up, p < 0.001). Daily off-times were reduced by 35%. Dyskinesias also improved markedly (UPDRS IV: 3.2/3.1 [on/off] vs. 0.9/1.3 at 12 months follow-up). Postoperative L-dopa medication was adjusted (mean reduction: 53%). Complications occurred in two patients (5%) who developed infections, leading to system removal. Systems were replaced after 6 months. Two patients (5%) had a permanent worsening of a previously known depressive state and developed progressive dementia. CONCLUSIONS: TN stimulation is a relatively safe procedure for treating advanced PD. The possibility of readjusting the stimulation parameters postoperatively improves the therapeutic outcome and reduces side effects in comparison to ablative methods.

Electric Stimulation Therapy↗

High frequency stimulation of the subthalamic nucleus eliminates pathological thalamic rhythmicity in a computational model.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or the internal segment of the globus pallidus (GPi) has recently been recognized as an important form of intervention for alleviating motor symptoms associated with Parkinson's disease, but the mechanism underlying its effectiveness remains unknown. Using a computational model, this paper considers the hypothesis that DBS works by replacing pathologically rhythmic basal ganglia output with tonic, high frequency firing. In our simulations of parkinsonian conditions, rhythmic inhibition from GPi to the thalamus compromises the ability of thalamocortical relay (TC) cells to respond to depolarizing inputs, such as sensorimotor signals. High frequency stimulation of STN regularizes GPi firing, and this restores TC responsiveness, despite the increased frequency and amplitude of GPi inhibition to thalamus that result. We provide a mathematical phase plane analysis of the mechanisms that determine TC relay capabilities in normal, parkinsonian, and DBS states in a reduced model. This analysis highlights the differences in deinactivation of the low-threshold calcium T -current that we observe in TC cells in these different conditions. Alternative scenarios involving convergence of thalamic signals in the cortex are also discussed, and predictions associated with these results, including the occurrence of rhythmic rebound bursts in certain TC cells in parkinsonian states and their drastic reduction by DBS, are stated. These results demonstrate how DBS could work by increasing firing rates of target cells, rather than shutting them down.

Action Potentials↗